Ondansetron, Alcohol Use, and Alcohol-Related Symptoms In HIV+ Persons

NCT ID: NCT01254877

Last Updated: 2018-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 357 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2017-01-31

Brief Summary

The proposed randomized clinical trial will investigate a novel pharmacotherapy for hazardous drinking, HIV-infected men and women, using the serotonin receptor (5-HT3) antagonist ondansetron. The investigators predict that participants who are treated with active doses of ondansetron will reduce their drinking more and show better HIV treatment participation and progress compared to participants who are treated with placebo. This study will provide important new safety and efficacy results on drinking and HIV outcomes following alcohol pharmacotherapy in HIV-infected persons.

Detailed Description

Hazardous drinking is particularly harmful in HIV-infected persons. It impairs the immune system, accelerates HIV disease progression, slows initiation of antiretroviral therapy (ART) and decreases adherence. Thus, the development of effective alcohol treatments for this clinical population is particularly important. The investigators are proposing to investigate the effectiveness of ondansetron pharmacotherapy for the treatment of hazardous alcohol use and alcohol abuse/dependence among HIV-infected patients. Ondansetron, a 5-HT3 antagonist, will be studied for several reasons: 1) evidence of effectiveness in persons who want to cut-down or reduce their drinking and who are not abstinent at medication initiation; 2) moderate-to-strong effects among early onset problem drinkers, a characteristic that is over represented in our clinic patients; 3) a very mild side-effect profile, making it an ideal pharmacotherapy candidate in patients who are often receiving multiple other medications with significant side-effects; and 4) its primary indication is for treatment of nausea, a common side-effect of antiretroviral (ARV) medications.

The proposed study is a placebo-controlled, randomized clinical trial of ondansetron for the treatment of hazardous drinking and alcohol use disorders among HIV-infected patients recruited from the Baltimore/Washington area. Participants will be genotyped for a functional polymorphism of the serotonin transporter gene. They will be randomized to one of three treatment groups: placebo, low dose ondansetron (0.2 mg bid) and moderate dose ondansetron (0.8 mg bid). All subjects will undergo 16 weeks of pharmacotherapy in combination with medication management, and will be followed for 3 and 6 months after medication has ended.

Conditions

Alcohol Abuse; Alcohol Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo Ondansetron - sugar pill

Placebo is an oral preparation made to appear and taste like the active drug preparation.

Group Type: PLACEBO_COMPARATOR

placebo ondansetron

Intervention Type: DRUG

Matching placebo will be prepared using a colorless strawberry syrup, simple syrup and flat Schweppes tonic water.

low dose ondansetron (0.2 mg bid)

Group Type: EXPERIMENTAL

ondansetron

Intervention Type: DRUG

ondansetron 0.2 mg bid, oral preparation, 16 weeks

moderate dose ondansetron (0.8 mg bid)

Group Type: EXPERIMENTAL

Ondansetron

Intervention Type: DRUG

Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration

Interventions

ondansetron

ondansetron 0.2 mg bid, oral preparation, 16 weeks

Intervention Type: DRUG

placebo ondansetron

Matching placebo will be prepared using a colorless strawberry syrup, simple syrup and flat Schweppes tonic water.

Intervention Type: DRUG

Ondansetron

Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects will be at least 18 years old and HIV-infected
• All subjects will be actively drinking at hazardous levels (1) AUDIT score => 4 for women or =>8 for men, or 2) => 2 binge drinking episodes/month, or 3) >7 drinks/week for women or >14 drinks/week for men)

Exclusion Criteria

• Liver Function Tests (LFTs) > 5 X normal
• Magnesium or potassium > 3 X normal
• Qtc => .460 and or a family history of long QT syndrome (LQT)
• Inability to read and comprehend English
• Actively psychotic or other severe mental health symptoms that would prevent appropriate participation
• Current enrollment in alcoholism treatment program
• Pregnancy; Ondansetron is currently a category B drug. While animal data have not identified any harmful effects to mother or fetus, there have not been adequate human controlled trials to recommend routine use in this population

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary E McCaul, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

References

Johnson BA, Roache JD, Javors MA, DiClemente CC, Cloninger CR, Prihoda TJ, Bordnick PS, Ait-Daoud N, Hensler J. Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial. JAMA. 2000 Aug 23-30;284(8):963-71. doi: 10.1001/jama.284.8.963.

Reference Type: BACKGROUND

PMID: 10944641 (View on PubMed)

Other Identifiers

R01AA018896

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00032774

Identifier Type: -

Identifier Source: org_study_id